Antibiotics in this group inhibit either the 30S or the 50S ribosomal subunit in bacteria.
Aminoglycosides and tetracyclines act on 30S ribosomes.
Aminoglycosides are bactericidal drugs effective against gram negative bacilli. Some are also active against Mycobacterium tuberculosis and Enterococci.
They bind to 16S rRNA of the 30S subunit near the A site through hydrogen bonds. This causes misreading of mRNA and premature termination of translation.
Because aminoglycosides are positively charged, they attach to the negatively charged outer membrane of bacteria. This leads to the formation of large pores that allow the drug to enter the bacterial cell. Entry requires oxygen-dependent active transport, so aminoglycosides are ineffective against anaerobic bacteria.
Aminoglycosides act synergistically with antibiotics that inhibit cell wall synthesis because cell wall disruption facilitates aminoglycoside entry into the cell. A classic example is gentamicin plus penicillin G to kill enterococci.
Tetracyclines are bacteriostatic drugs with activity against gram positive and gram negative bacteria, chlamydia, rickettsia, and mycoplasma. This group includes tetracycline, chlortetracycline, doxycycline, and minocycline.
They bind to 16S rRNA of the 30S bacterial ribosomal subunit and prevent binding of tRNA to the A site.
Tigecycline is a glycylcycline that is structurally similar to tetracyclines and has the same mechanism of action. It is used to treat MSSA and MRSA skin and subcutaneous infections, group A and B streptococci, E coli, Bacteroides fragilis, and intra abdominal infections caused by facultative and anaerobic bacteria.
Chloramphenicol, oxazolidinones, and macrolides are major classes of drugs that inhibit 50S ribosomes.
Chloramphenicol is a broad spectrum antibiotic effective against gram positives, gram negatives, and anaerobes. It may be bacteriostatic (Salmonella typhi) or bactericidal (H influenzae, N meningitidis and S pneumoniae).
It binds to 23S rRNA of the 50S subunit, inhibiting peptidyl transferase activity, and prevents binding of tRNA to the A site of the ribosome.
These three groups of antibiotics have a similar mechanism of action in inhibiting bacterial protein synthesis. They affect translocation by inhibiting the peptidyl transferase activity of 23S rRNA of the 50S ribosomal subunit. This causes premature detachment of incomplete peptide chains.
Macrolides are wide spectrum bacteriostatic drugs that include azithromycin, erythromycin, and clarithromycin. Azithromycin and erythromycin are used to treat Chlamydia trachomatis and respiratory tract infections caused by Legionella, Mycoplasma, Chlamydia pneumoniae, and S pneumoniae. Clarithromycin is used in the treatment of H pylori and Mycobacterium avium intracellulare.
Lincosamides include lincomycin, pirlimycin, and clindamycin. They are bacteriostatic drugs used to treat gram positive bacteria only, because they cannot pass through the pores of gram negative bacteria.
Streptogramins include quinipristin/dalfopristin, pristinamycin, and virginiamycin. They are used in the treatment of VRSA (vancomycin resistant S. aureus) and VRE (vancomycin resistant enterococci).
Linezolid is effective against VRE, MRSA, and MRSE (methicillin resistant S.epidermidis), and penicillin resistant pneumococci. It interferes with protein synthesis at 23S rRNA of the 50S subunit and inhibits peptidyl t RNA.
Retapamulin is a newer antibiotic used topically for skin infections caused by streptococci (impetigo) and staphylococci. It binds to 23S rRNA of the 50S subunit and blocks the attachment of the donor tRNA.
Quinolones are included in this group. They are bactericidal drugs, including ofloxacin, levofloxacin, ciprofloxacin, norfloxacin, etc. They are effective against organisms causing lower respiratory tract infections, gastrointestinal infections, UTIs, and skin, bone, and soft tissue infections.
They inhibit the enzyme DNA gyrase in bacteria, also called topoisomerase IV. They specifically target the “A” subunit of the enzyme and interfere with its strand cutting and resealing function, thereby inhibiting DNA replication.
This group includes sulfonamides and trimethoprim. In combination, these drugs are effective in the treatment of toxoplasmosis, Pneumocystis jiroveci pneumonia, UTIs, and shigellosis.
Each drug inhibits a distinct step in folic acid metabolism, leading to inhibition of tetrahydrofolate synthesis. Tetrahydrofolate is essential for nucleic acid synthesis in bacteria.
Sulfonamides are structural analogues of PABA (para aminobenzoic acid), which is a substrate for the enzyme dihydropteroate synthase. Sulfonamides therefore competitively inhibit this enzyme.
Trimethoprim inhibits dihydrofolate reductase, a later step in folic acid synthesis.
The combination of sulfonamides with trimethoprim shows synergy in inhibiting bacterial growth and also lowers the emergence of resistant bacterial mutants.
Rifampin and rifabutin belong to this group. They block mRNA synthesis by bacterial RNA polymerase.
Rifampin is used in the treatment of tuberculosis, S.epidermidis prosthetic valve endocarditis, and prophylaxis of N.meningitidis and H. influenzae meningitis. Rifabutin is used in the prophylaxis of M.avium-intracellulare infections in AIDs patients.
This group includes polymyxins and daptomycin.
Polymyxins B and E (colistin) Polymyxins B and E (colistin) are effective against gram negative bacilli. They bind to lipopolysaccharides in the outer membrane of gram negative bacteria and act as a cationic detergent to disrupt the phospholipid structure of the cell membrane.
Daptomycin (Cubicin) Daptomycin (Cubicin) is a lipopeptide antibiotic effective against a wide range of gram positive cocci such as S.aureus and S.epidermidis, including resistant strains like MRSA, MRSE, and VRSA; and Enterococcus faecalis and faecium, including resistant strains like VRE.
Because of its efficacy against resistant bacterial strains, it is used in the treatment of skin and soft tissue infections caused by these bacteria, and sometimes in endocarditis and sepsis. It inserts into the bacterial cell membrane, creating holes that cause ions to leak from the cell. This leads to rapid depolarization and resultant inhibition of protein and nucleic acid synthesis.